Cadherines and catenines form cell adhesion complexes, which are responsible in numerous tissues for the adhesion of cells to one another. The cadherines are trans-membrane proteins and produce the direct contact between adjacent cells. α-, β- and γ-catenine are cytoplasmic components, which connect the cadherines with the actin cytoskeleton. Aside from their function in cell adhesion, the catenines also play a decisive role in signal transduction processes. β-Catenine in vertebrates and the homologous, segment polarity gene product, armadillo in drosophila, are stabilized by the Wnt/wingless signal path (Nusse, R., Cell 89, 321–323, 1997). This leads to an increase in the cytoplasmic fraction of these proteins, which is not bound to cadherine, which thereupon could interact with HMG transcription factors of the LEF-1/TCF families. As a result, β-catenine/armadillo is transported into the cell nucleus where, together with the LEF/TCF proteins, it binds to the DNA and activates certain genes (Behrens, J. et al., Nature 382, 638–642, 1996).
This signal path also plays an important role in the formation of tumors. In epithelial cells of the colon, the cytoplasmic pool of β-catenine is strictly regulated by the tumor suppressor gene product APC (Adenomatosis Polyposis Coli). Mutations of APC, such as those occurring in 80% of all colon cancers, lead to shortened forms of the APC protein, which are no longer able to destabilize β-catenine. As a result, permanent complexes of β-catenine with the HMG transcription factor TCF-4, which are asserted to be responsible for the transformation of the cells, are found in these tumors. This theory is supported by the recent finding that, in tumors in which APC is not changed, mutations of β-catenine occur. These also lead to cytoplasmic stabilization of β-catenine and to an association with LEF-1/TCF factors (Morin, P. J. et al., Science 275, 1787–1790).